Expansion mutation in C9ORF72 does not influence plasma progranulin levels in frontotemporal dementia

Neurobiol Aging. 2012 Aug;33(8):1851.e17-9. doi: 10.1016/j.neurobiolaging.2012.03.005. Epub 2012 Apr 11.


A hexanucleotide repeat expansion in chromosome 9 open reading frame 72 (C9ORF72) gene has recently been described as a cause of familial and sporadic frontotemporal lobar degeneration. The aim of this study was to assess whether plasma progranulin (GRN) levels could be modulated by the presence of this repeat expansion. Sixty-five patients diagnosed with frontotemporal dementia and 10 family members with familial aggregation of disease were screened for the presence of the hexanucleotide repeat expansion in C9ORF72 gene, using a repeat-primed polymerase chain reaction method. Plasma GRN levels were measured in all subjects through enzyme-linked immunosorbent assay. Seven individuals with the repeat expansion were identified. No differences were found between C9ORF72 repeat expansion carriers and noncarriers (116.4 ± 21 ng/mL and 131.7 ± 36 ng/mL, respectively, p = 0.3). Analysis of family members did not disclose any difference in plasma GRN levels between carriers and noncarriers. In conclusion, plasma GRN levels are not influenced by the hexanucleotide repeat expansion in C9ORF72 gene, and therefore, cannot be used as a reliable biomarker to detect mutation carriers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Frontotemporal Dementia / blood*
  • Frontotemporal Dementia / epidemiology
  • Frontotemporal Dementia / genetics*
  • Genetic Markers / genetics
  • Genetic Predisposition to Disease / epidemiology
  • Genetic Predisposition to Disease / genetics
  • Genetic Variation / genetics
  • Humans
  • Intercellular Signaling Peptides and Proteins / blood*
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Prevalence
  • Progranulins
  • Protein Serine-Threonine Kinases / genetics*
  • Repetitive Sequences, Nucleic Acid / genetics*
  • Risk Factors
  • Spain / epidemiology


  • GRN protein, human
  • Genetic Markers
  • Intercellular Signaling Peptides and Proteins
  • Progranulins
  • LRRK2 protein, human
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Protein Serine-Threonine Kinases